MONOCLONAL-ANTIBODY LU-BCRU-G7 AGAINST A BREAST TUMOR-ASSOCIATED GLYCOPROTEIN RECOGNIZES THE DISACCHARIDE GAL-BETA-1-3GLCNAC

被引：42

作者：

RYE, PD

BOVIN, NV

VLASOVA, EV

WALKER, RA

机构：

[1] RUSSIAN ACAD SCI,MM SHEMYAKIN BIOORGAN CHEM INST,MOSCOW 117871,RUSSIA

[2] UNIV LEICESTER,GLENFIELD GEN HOSP,BREAST CANC RES UNIT,LEICESTER LE3 9QP,LEICS,ENGLAND

来源：

GLYCOBIOLOGY | 1995年 / 5卷 / 04期

关键词：

CANCER; GAL-BETA-1-3GLCNAC; LU-BCRU-G7; MONOCLONAL ANTIBODY; PSEUDOPOLYSACCHARIDES;

D O I：

10.1093/glycob/5.4.385

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The monoclonal antibody LU-BCRU-G7, that was generated by in vitro immunization, shows clinical value as a prognostic marker in early stage breast carcinoma, It has now been characterized with regard to its binding epitope, Using a recently described method based on the construction of N-substituted polyacrylamide (PAA) derivatives of carbohydrates (pseudopolysaccharides), the structure of the epitope for the monoclonal antibody LU-BCRU-G7 has been determined, Competitive binding assays and inhibitory enzyme-linked inmunosorbent assays (ELISAs) using these pseudopolysaccharides have shown the LU-BCRU-G7 epitope to be a disaccharide Gal beta 1-3GlcNAc (Le(c); where Gal is D-galactose, Glc is D-glucose and GlcNAc is N-acetyl-D-glucosamine). Both galactose and N-acetyl glucosamine moieties are essential for binding, Substitution on C-2 or C-3 of the terminal galactose abolished binding, as did galactose-alpha terminated oligosaccharides, The galactose moiety alone, as expressed by the Gal beta-PAA conjugate, appeared to be a more important feature of the epitope than the GlcNAc-PAA conjugate, which failed to bind or inhibit the LU-BCRU-G7 antibody, In the N-acetyl glucosamine moiety, binding was decreased but not eliminated by fucose substitution, as in Le(a), or change in configuration of C-4, as in Gal beta 1-3GlcNAc. Omission of the NAc group resulted in complete loss of activity, The tetrasaccharide lacto-N-tetraose, although containing the terminal Le(c) disaccharide, does not react with the antibody, suggesting conformational interference of the binding site, These findings show that the monoclonal antibody LU-BCRU-G7 recognizes a terminal isolactosamine fragment on a tumour-associated glycoprotein, which we have previously shown to be inversely related to survival in breast cancer.

引用

页码：385 / 389

页数：5

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